D+Q+F+P+L+G+GLA: A New Senolytic Cocktail
For my May 15-18 senolytic session I tried something new. In a recent Foresight Institute talk available on YouTube, James Kirkland identified the flavonoid Luteolin as a senolytic. There have also been reports that GLA and Gingerenone have strong senolytic properties. Therefore, on the theory that in a senolytic session the more different senolytics the merrier, I decided to combine these three with the D+Q+F+P senolytics that I has already been using. It is not clear how much of the new items one should take, so I had to guess. And so, in late mornings of this past Sunday, Monday, and Wednesday I took the following senolytic cocktail:
1 x 50 mg Dasatinib (From India; I usually take 100-200 mg, but only 3 tabs left)
4 x 475 mg Quercetin (Swanson)
10 x 44.5 mg Bio-Fisetin (Life Extension protected caps with x25 bioavailability)
1 x 10 mg Bioperine (Swanson)
8 x 165 mg Luteolin (Geroprotect Autophagy Renew)
10 x 200 mg Ginger Root Extract (Swanson, Gingerenone amount unknown)
5 x 400 mg Mega GLA (Life Extension, with 10 mg Sesame Lignans)
That’s a dismayingly large number of tablets and capsules, but for these three sessions I took them with water all in one sitting. On Sunday evening following the first session I experienced a mild headache, mild intestinal cramps, and a feeling of unwellness. On Monday evening I experienced stronger versions of these symptoms, plus frequent bowel movements and a mild fever. On Tuesday I was scheduled for a 12:15 PM dog-agility training class, and I felt unwell enough that I almost skipped it. My performance at class was sub-par. When I returned home from it, I decided to defer the final Tuesday senolytic session by a day. I went directly to bed and took a long nap. On Wednesday I felt better, and I did the final senolytic session at about 11 AM. This time the side-effects were not as strong, but I had a bowel movement that included a rather strong burning sensation, which I suspect was due to the exit of the Ginger Root Extract. While I was sleeping last night from 3-7 AM I experienced mild intestinal cramps. On Thursday (today) all the negative symptoms are gone, and I feel very well and energetic, with no bodily aches and pains at all.
I attribute the negative side effects described above to (a) the residue of cleared senescent cells in my bloodstream and (b) the presence in my digestive system of molecules that are usually not present and are temporarily producing intestinal inflammation and cramping (and clearing senescent intestinal cells). The observed effects were quite a bit stronger than I had experienced with D+Q+F+P sessions in October and in February, and I think the three added ingredients are achieving increased senolytic action and perhaps are clearing senescent cells of more diverse cell types. I take the mild headaches as an indication that senolytic molecules are getting past the blood-brain barrier.
All in all, I think my experiment was a success. I plan to repeat the use of this cocktail for my next sessions in August.
I think you need to do more frequent sessions.
Dr Green takes dasatinib and fisetin every 2 weeks.
I think that is a bit too frequent, but people report return of inflammation that the senolytics alleviated after about 3-4 weeks.
So I think monthly sessions are more optimal versus a few times per year.
Geroprotect Autophagy Renew is an interesting product. This since it is one of the few products that contain piperlongumine.
I think it is a substance that could use at lot more attention since it has many interesting properties. One that comes to my mind is the effect on prostate tissues. It blocks the androgen receptor as well as induce apoptosis in many cancerous cell lines. Another nice property is its good bioavailability and the low threshold to reach therapeutic levels.
”PL appears to be very safe, and its maximum tolerated oral dose in mice is >1 g/kg, while the effective therapeutic doses for cancer can be as low as 2.4 mg/kg by oral dosing." If 2,4 mg/kg is translated to the human the equivalent, then 2,4 mg/kg in mice will be 2,4/12,3=0,195 mg/kg for a human. For a 80 kg person this means 80*0,195 mg =15,6 mg. to reach a therapeutic threshold for cancer treatment. So if you take 8 geroprotect autophagy renew then you take a dose of 80 mg piperlongumines.
80 mg looks like a massive dose! Have you noticed any change in urodynamics?
"Another potential use of PL and its derivatives is in combination with ABT-263, or other inhibitors of Bcl-2 family proteins, for a synergistic senolytic effect. Although ABT-263 is a highly specific senolytic agent, it causes transient thrombocytopenia and neutropenia in patients this results from its inhibitory effect on Bcl-xL, which is important for platelet survival. We showed that PL had a strong synergistic effect on the senolytic activity of ABT-263 in vitro, potentially reducing the dose of ABT-263 needed to effectively deplete SCs. We expect this therapeutic approach would significantly reduce ABT-263-induced thrombocytopenia, making senolytic treatment with ABT-263 safer.”
My personal exepience is from me taking at the most 3-4 geroprotect autophagy renew = 30 - 40 mg piperlongumine. I have taken the Geroprotect with theflavines (which are thought to be an inhibitor of BCL-2 ) which I bought from life extension. I also take it woth quercetin from thorne. My anecdotal experience is that PL works well for me.
One thing to keep in mind is that PL works in many ways. In ROS dependent ways as well as in ROS independent ways In some cancer research the positive effect of PL has been eradicated by n- Acetyl cysteine.
That makes sense, but what would happen if you increased your treatment frequency to, say, once a month?...roughly the amount of time it takes for a senescent cell to start secreting SASP (and affecting adjacent cells). Think you would help break (or substantially slow down) the senescent cell production cycle associated with SASP exposure from adjacent senescent cells. Do you think this might, also, be physically verified by less fever-like reactions (and headaches?) from the more frequent interventions?...would be interesting to find out.
Remember reading that on Dr. Green's senescence-related website (https://senolyticstreatment.com/) regarding the time-line from senescence to SASP. It's too bad about the discomfort at your present rate/schedule though. Quality of life is important too.
Am guessing you don't subscribe to inhibiting your mTORC1 (e.g. taking Rapamycin) which reduces senescence rate ~ 3-fold?
A reliable (and relatively well reviewed) supplier is Towada Products via Indiamart--Ravinder Gandhi is the contact there. They offer several manufacturers, but recommend Biocon (Rapacan1) since they are better known than the rest. Remember buying 400 x 1mg for a little over $440 including shipping last year, so it's also very reasonable...but you'll have to wait roughly 3 weeks or so for delivery.
Here's the link: https://www.indiamart.com/towadaproducts/search.html?ss=sirolimus
Hi, team. It's Dr. Mark McGovern, an Australian plastic surgeon interested in anti-ageing (yes, that is how it is spelt in English) medicine. I can vouch for the apparent reliability and efficacy of an Indian brand of dasatinib, being Dasakast-70 by manufacturer Aprazer Healthcare in New Delhi. I am 90 kg and took 4 x 70 mg tablets initially, with somewhat incapacitating GI symptomatology initially. At a dose of 210mg, I just get mild diahorrea for a couple of days. As for rapamycin, in Australia I can write myself a script for 100 tablets of 1 mg Rapamune (Pfizer) for A$41.30, i.e. about US $30. I am using 2,500 mg quercetin with my 3 monthly 210mg dasatinib and 100mg fisetin, the latter from Life Extension. Is there data supporting a higher fisetin dose? Cheers, Mark.
Is there any way of measuring senescent cells in the human body? I am afraid we may be poisoning ourselves without a proper way to measure to see what is happening to our bodies. Feelings can be deceptive as many feel great after recovering from major illness, but it is doubtful if the illness was beneficial. The best forms of proof for me would be hair regrowth or spot removal (i.e. liver spots) or some other physiological change that can be measured. Is there anything out there to prove senescent cell removal in vivo? Thanks...
I've long been fond of CRP testing, and short of more accurate & inexpensive tests to measure senolytic activity, it may be best. However, almost all medicine & even holistic drug recommendations are based on weight. Far more accurate, & useful, would be to include age, health conditions, etc. For instance, CRP is mostly to catch over-all inflammation, which is likely root of all disease & aging, but shouldn't individuals with cancer, take more -- and/or more frequent -- dosing?
Separately, maybe 30 years ago, as an LEF member, I did blood work through them, and despite checking the appropriate boxes, LEF used my blood results in a study (I found out through another error by LEF.) And with LEF, publishing my results -- even without my ID -- is with purpose of selling various LEF products. That & other experiences, have resulted in my not trusting LEF, although I still use some of their products, although buying from AMZN is same price as being an LEF member